The aim of this study was to evaluate effects of aqueous extract from Cortex acanthopanacis (CAE) on osteoporosis rats induced by ovariectomy (OVX) using aqueous extract from Folium Epimedii (FEE) as positive control agent. Three-month-old female rats that underwent OVX were treated with CAE. After 12 weeks, bone mineral density (BMD) and indices of bone histomorphometry of tibia were measured. Levels of protein and mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) in tibia were evaluated. In addition, the serum concentrations of osteocalcin (OC), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), calcitonin (CT), and parathyroid hormone (PTH) were determined. Administration of CAE significantly prevented OVX-induced rats from gain of the body weight. Treatment with CAE increased bone mass remarkably and showed a significant inhibitory effect on bone resorption by downregulating significantly the expression of RANKL in tibia of OVX rats. Meanwhile, treatment of CAE significantly reduced serum level of IL-1β and increased level of CT in OVX rats. This suggests that CAE has the potential to be used as an alternative therapeutic agent for postmenopausal osteoporosis.